From the Journals

Guidelines released for perimenopausal depression

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Recognize symptoms of perimenopausal depression

I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.

Dr. Jan Leslie Shifren

Dr. Jan Leslie Shifren

Postpartum depression syndrome has been very well characterized, with clear guidelines for diagnosis and treatment. But researchers have identified the menopausal transition as another window of vulnerability for women, another time of dramatic hormonal fluctuations. People often think of perimenopause as a gradual decline in estrogen levels, but it is a time when there can be very high estrogen levels followed by very low estrogen levels. Because of this unpredictability, it makes sense that this is another time period that needs to be well studied.

There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.

The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.

Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.

Jan Leslie Shifren, MD , is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.



Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.

Woman looking sad. pixelheadphoto/ThinkStock

“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”

The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.

Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.

Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.

Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.

Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.

“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”

Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.

There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.

Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.

The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”

Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.

SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.

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